School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
Hunter Medical Research Institute, Newcastle, Australia.
Sci Rep. 2019 Mar 19;9(1):4841. doi: 10.1038/s41598-019-39493-8.
In the current study, we were interested in investigating whether Low oxygen post-conditioning (LOPC) was capable of limiting the severity of stroke-induced secondary neurodegeneration (SND). To investigate the effect of LOPC we exposed adult male C57/BL6 mice to photothrombotic occlusion (PTO) of the motor and somatosensory cortex. This is known to induce progressive neurodegeneration in the thalamus within two weeks of infarction. Two days after PTO induction mice were randomly assigned to one of four groups: (i) LOPC-15 day exposure group; (ii) a LOPC 15 day exposure followed by a 15 day exposure to normal atmosphere; (iii) normal atmosphere for 15 days and (iv) normal atmosphere for 30 days (n = 20/group). We observed that LOPC reduced the extent of neuronal loss, as indicated by assessment of both area of loss and NeuN cell counts, within the thalamus. Additionally, we identified that LOPC reduced microglial activity and decreased activity within the excitotoxic signalling pathway of the NMDAR axis. Together, these findings suggest that LOPC limits neuronal death caused by excitotoxicity in sites of secondary damage and promotes neuronal survival. In conclusion, this work supports the potential of utilising LOPC to intervene in the sub-acute phase post-stroke to restrict the severity of SND.
在目前的研究中，我们有兴趣研究低氧后处理（LOPC）是否能够限制中风引起的继发性神经退行性病变（SND）的严重程度。为了研究 LOPC 的效果，我们使成年雄性 C57/BL6 小鼠暴露于光血栓性大脑皮层运动和躯体感觉区阻塞（PTO）。已知这会在梗塞后两周内导致丘脑内进行性神经退行性变。PTO 诱导后两天，将小鼠随机分配到以下四个组之一：（i）LOPC-15 天暴露组；（ii）LOPC 15 天暴露后再暴露于正常大气 15 天组；（iii）正常大气暴露 15 天组和（iv）正常大气暴露 30 天组（每组 n=20）。我们观察到，LOPC 减少了丘脑内神经元丢失的程度，这表明通过评估损失面积和 NeuN 细胞计数得到了证实。此外，我们发现 LOPC 降低了小胶质细胞的活性，并降低了 NMDAR 轴兴奋毒性信号通路的活性。总之，这些发现表明，LOPC 限制了继发性损伤部位兴奋性毒性引起的神经元死亡，并促进了神经元的存活。总之，这项工作支持利用 LOPC 在中风后亚急性期进行干预，以限制 SND 的严重程度的潜力。
